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 Printable version |
Towards a rational classification of hereditary iron overload and hyperferritinaemia |
Hématologie. Volume 10, Number 4, 275-85, Juillet-août 2004, Revue
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 Résumé
Article gratuit
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Author(s) : Patricia Aguilar Martinez Jean‐François Schved |
Summary : Since the description in 1996 of the
HFE gene, the main gene responsible for hereditary hemochromatosis (HH), an increasing number of new genes implicated in iron metabolism have been discovered. Some of these genes are involved in hereditary iron overload or hereditary hyperferritinaemia. A rational diagnostic strategy is needed to approach these molecular defects associated to human diseases. The strategy we propose is based on the age of outcome of the symptoms, on the type of clinical signs and on the biological tests (hyperferritinaemia alone or associated with raised transferrin saturation), and finally upon the family transmission (autosomal recessive or dominant). These characteristics allow the differentiation of three clinical forms. The most frequent is the classical’ form of hereditary hemochromatosis linked to the
HFE gene, and rarely to mutations of the
TFR2 gene. Juvenile hemochromatosis is a rare and severe form of iron overload diagnosed in young adults (<\; 30 years). It is due to mutations in two recently described genes, the gene
HJV, coding for hemojuvelin, and the
HAMP gene, coding for the protein hepcidin. Both, the adult and the juvenile type, have an autosomal recessive transmission. Lastly, hereditary hyperferritinaemias can be associated or not with iron overload. They are transmitted on an autosomal dominant manner. Hereditary hyperferritinaemia without iron overload corresponds to the hereditary hyperferritinaemia cataract syndrome due to mutations in the 5’UTR region of the L‐ferritin gene. Hyperferritinaemia associated with mutations in the
SLC40A 1 gene, coding for ferroportin 1, seems to be more frequent than it was thought initially. Mutations of this gene have been recently implicated in African iron overload. The classification into these three clinical forms seems interesting for the diagnostic approach, although it is undoubtedly that new genes remain to be described. |
Keywords : hereditary hemochromatosis, hyperferritinaemia, gene classification |
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